1. Field of the Invention
This invention relates to the preparation of heterocyclic aminomethylene compounds by the reaction of aminopyridines with malonic acid derivatives and orthoformic acid trialkyl esters.
More particularly, this invention relates to the preparation of pyridylaminomethylenemalonic acid derivatives by a one-step process in which an aminopyridyl compound is reacted together with orthoformic acid trialkyl esters and a malonic ester. The present invention is particularly directed to the preparation of pyridylaminomethylenemalonic acids in high yields in excess of 90%.
2. Discussion of the Prior Art
It is known that, in the reaction of aminopyridines with alkoxymethylenemalonic acid esters that pyridylaminomethylenemalonic acid esters are formed together with alcohol. (cf. G. Lappin). Pursuant to such prior art processes, there is obtained yields which amount to about 90% as disclosed in Chemical Abstracts, Volume 66, page 268 (1967). The alkoxylmethylene malonic acid esters which are required for this reaction are prepared in a separate procedure or the condensation of orthoformic acid esters with compounds containing active methylene groups, in the presence of a catalyst. Condensation catalysts employed include acetic acid anhydride and, when malonic esters are used, anhydrous zinc chloride as well (cf. Berichte 26, 2729 (1893) and Annalen 279, 16 (1897). In this known process there is necessarily involved two reaction steps for the formation of the pyridylaminomethylenemalonic compounds. These reaction steps are as follows:
1. Initially the alkoxymethylene compound is prepared from orthoformic acid esters and malonic acid derivatives in the presence of a catalyst. The products that form are isolated generally by a fractional distillation process carried out in a fine vacuum column. The yields in this step of the desired alkoxymethylene compounds run between 65 and 85% of theory, based upon the malonic ester derivative.
2. After the alkoxymethylene compound is separated from the first step, it is condensed with aminopyridines.
As a result of this two-step process the yield per unit volume per unit of time is low and the yield of end product, referred to the malonic acid ester input, is only about 60 to 75% of theory.
Accordingly, it became desirable to provide a process wherein the yield of pyridylaminomethylenemalonic acid derivative, referred to the malonic acid ester input was substantially better than 75%. Moreover, it became desirable to provide a one-step process for the synthesis of such pyridylaminomethylenemalonic acid derivatives from aminopyridine compounds, orthoformic acid esters and esters of malonic acid. It became desirable to provide such a process which could be carried out in the absence of a catalyst.